Chapter 13-Reactive (Inflammatory) Proliferations of White Cells & Lymph Nodes

Question 1

What is leukocytosis?

Answer 1

Leukocytosis refers to an increase in the number of white cells in the blood . It is a common
reaction to a variety of inflammatory states.

Question 2

What is the pathogenesis of Leukocytosis?

Answer 2

Pathogenesis.
The peripheral blood leukocyte count is influenced by several factors, including:

• • The size of the myeloid and lymphoid precursor and storage cell pools in the bone marrow, thymus, circulation, and peripheral tissues
• • The rate of release of cells from the storage pools into the circulation
• • The proportion of cells that are adherent to blood vessel walls at any time (the marginal pool)
• • The rate of extravasation of cells from the blood into tissues

Question 3

What maintains the hemostasis of

Answer 3

leukocyte homeostasis is maintained by cytokines, growth factors, and adhesion molecules through their effects on the commitment, proliferation,
differentiation, and extravasation of leukocytes and their progenitors

Question 4

In acute infection there is a rapid increase in the egress of mature granulocytes from the bone marrow pool.

What happens when the infection is prolonged?

Answer 4

If the infection is prolonged, the release of interleukin-1 (IL-1), tumor necrosis factor (TNF), and other inflammatory cytokines stimulates bone marrow stromal cells and T cells to produce increased amounts of hematopoietic growth factors, which enhance the proliferation and differentiation of committed granulocytic progenitors and, over several
days, cause a sustained increase in neutrophil production.

Question 5

TABLE 13-2 – Mechanisms and Causes of Leukocytosis

INCREASED PRODUCTION IN THE MARROW

Answer 5

• Chronic infection or inflammation (growth factor-dependent)
• Paraneoplastic (e.g., Hodgkin lymphoma; growth factor-dependent)
• Myeloproliferative disorders (e.g., chronic myeloid leukemia; growth factorindependent)

Question 6

TABLE 13-2 – Mechanisms and Causes of Leukocytosis

INCREASED RELEASE FROM MARROW STORES

Answer 6

• Endotoxemia
• Infection
• Hypoxia

Question 7

TABLE 13-2 – Mechanisms and Causes of Leukocytosis

DECREASED MARGINATION

Answer 7

Exercise
Catecholamines

Question 8

TABLE 13-2 – Mechanisms and Causes of Leukocytosis

DECREASED EXTRAVASATION INTO TISSUES

Answer 8

Glucocorticoids

Question 9

Some growth factors preferentially stimulate the production of a single type of leukocyte.

For example, IL-5 mainly stimulates_________,

Answer 9

eosinophil production

Question 10

Some growth factors preferentially stimulate the production of a single type of leukocyte.

G-CSF induces ___________

Answer 10

neutrophilia.

Question 11

TABLE 13-3 – Causes of Leukocytosis

Neutrophilic
leukocytosis

Answer 11

• Acute bacterial infections, especially those caused by pyogenic organisms;
• sterileinflammation caused by, for example, tissue necrosis (myocardial infarction, burns)

Question 12

TABLE 13-3 – Causes of Leukocyosis

Eosinophilic leukocytosis
(eosinophilia)

Answer 12

• Allergic disorders such as asthma, hay fever;
• certain skin diseases (e.g., pemphigus, dermatitis herpetiformis); parasitic infestations;
• drug reactions;
• certain malignancies (e.g., Hodgkin and some non-Hodgkin lymphomas);
• collagen vascular disorders and some vasculitides; atheroembolic disease (transient)

Question 13

TABLE 13-3 – Causes of Leukocyosis

Basophilic
leukocytosis
(basophilia)

Answer 13

Rare, often indicative of a myeloproliferative disease (e.g., chronic myeloid leukemia)

Question 14

TABLE 13-3 – Causes of Leukocyosis

Monocytosis

Answer 14

• Monocytosis Chronic infections (e.g., tuberculosis), bacterial endocarditis, rickettsiosis, and
• malaria; collagen vascular diseases (e.g., systemic lupus erythematosus);
• inflammatory bowel diseases (e.g., ulcerative colitis)

Question 15

TABLE 13-3 – Causes of Leukocyosis

Lymphocytosis

Answer 15

• Accompanies monocytosis in many disorders associated with chronic immunological stimulation (e.g., tuberculosis, brucellosis);
• viral infections (e.g., hepatitis A, cytomegalovirus, Epstein-Barr virus);
• Bordetella pertussis infection

Question 16

What are Döhle bodies

Answer 16

I.

Toxic granules, which are coarser and darker
than the normal neutrophilic granules, represent abnormal azurophilic (primary) granules.

Döhle bodies are patches of dilated endoplasmic reticulum that appear as sky-blue cytoplasmic
“puddles

Question 17

Where can you find Döhle
bodies, and cytoplasmic vacuoles ?

Answer 17

In sepsis or severe inflammatory disorders (such as Kawasaki disease), leukocytosis is often
accompanied by morphologic changes in the neutrophils, such as toxic granulations, Döhle
bodies, and cytoplasmic vacuoles ( Fig. 13-2 )

Question 18

Answer 18

FIGURE 13-2 Reactive changes in neutrophils.

Neutrophils containing coarse purple
cytoplasmic granules (toxic granulations) and blue cytoplasmic patches of dilated endoplasmic reticulum (Döhle bodies, arrow) are observed in this peripheral blood smear prepared from a patient with bacterial sepsis

Question 19

In most instances it is not difficult to distinguish reactive and neoplastic leukocytoses, but
uncertainties may arise in two settings.

Answer 19

• Acute viral infections, particularly in children, can cause the appearance of large numbers of activated lym phocytes that resemble neoplastic lymphoid cells.
• At other times, particularly in severe infections, many immature granulocytes appear in the blood, simulating a myeloid leukemia (leukemoid reaction) .

Special laboratory studies (discussed later) are helpful in distinguishing reactive and neoplastic leukocytoses.

Question 20

What is a leukemoid reaction?

Answer 20

At other times, particularly in severe infections, many immature granulocytes appear in the blood, simulating a myeloid leukemia (leukemoid reaction) .

Question 21

Following their initial development from precursors in the bone marrow (B cells) and the thymus (T cells), lymphocytes circulate through the blood and, under the influence of specific cytokines
and chemokines, home to lymph nodes, spleen, tonsils, adenoids, and Peyer’s patches, which
constitute the peripheral lymphoid tissues.

Question 22

What is the most widely distributed and easily
accessible lymphoid tissue?

Answer 22

Lymph nodes, the most widely distributed and easily
accessible lymphoid tissue, are frequently examined for diagnostic purposes.

They are discrete encapsulated structures that contain well-organized B-cell and T-cell zones, which are richly
invested with phagocytes and antigen-presenting cells ( Fig. 6-6 , Chapter 6 ).

Question 23

What happens when there is activation of resident immune cells?

Answer 23

The activation of resident immune cells leads to morphologic changes in lymph nodes

• Within several days of antigenic stimulation, the primary follicles enlarge and are transformed into pale-staining germinal centers, highly dynamic structures in which B cells acquire the capacity to make high-affinity antibodies against specific antigens.
• Paracortical T-cell zones may also undergo hyperplasia.

The degree and pattern of the morphologic changes are dependent on
the inciting stimulus and the intensity of the response. Trivial injuries and infections induce
subtle changes, while more significant infections inevitably produce nodal enlargement and sometimes leave residual scarring.

For this reason, lymph nodes in adults are almost never “normal” or “resting,” and it is often necessary to distinguish morphologic changes secondary to
past experience from those related to present disease.

Infections and inflammatory stimuli often
elicit regional or systemic immune reactions within lymph nodes.

Some that produce distinctive
morphologic patterns are described in other chapters. Most, however, cause stereotypical
patterns of lymph node reaction designated acute and chronic nonspecific lymphadenitis.

Question 24

What are Acute Nonspecific Lymphadenitis?

Answer 24

Acute lymphadenitis in the cervical region is most often due to microbial drainage from
infections of the teeth or tonsils, while in the axillary or inguinal regions it is most often caused
by infections in the extremities .

Acute lymphadenitis also occurs in mesenteric lymph nodes draining acute appendicitis.

Unfortunately, other self-limited infections may also cause acute mesenteric adenitis and induce symptoms mimicking acute appendicitis, a differential diagnosis
that plagues the surgeon.

Systemic viral infections (particularly in children) and bacteremia
often produce acute generalized lymphadenopathy.

Question 25

What is the gross morphology of Acute Nonspecific Lymphadenitis?

Answer 25

Grossly, the nodes are swollen, gray-red, and engorged.

Question 26

What is the microscopic morphology of Acute Nonspecific Lymphadenitis?

Answer 26

Microscopically,

• there is prominence of large reactive germinal centers containing numerous mitotic figures.
• Macrophages often contain particulate debris derived from dead bacteria or necrotic cells.
• When pyogenic organisms are the cause, the centers of the follicles may undergo necrosis; sometimes the entire node is converted into a bag of pus.
• With less severe reactions, scattered neutrophils infiltrate about the follicles and accumulate within the lymphoid sinuses.
• The endothelial cells lining the sinuses undergo hyperplasia.

Question 27

Clinically nodes involved by acute lymphadenitis are what?

Answer 27

• Nodes involved by acute lymphadenitis are enlarged and painful.
• When abscess formation isextensive the nodes become fluctuant.
• The overlying skin is red.
• Sometimes, suppurative infections penetrate through the capsule of the node and track to the skin to produce draining sinuses.
• Healing of such lesions is associated with scarring.

Question 28

Chronic Nonspecific Lymphadenitis

Chronic immunological stimuli produce several different patterns of lymph node reaction

Answer 28

• Follicular hyperplasia
• Paracortical hyperplasia
• Sinus histiocytosis (also called reticular hyperplasia)

Question 29

What causes follicular hyperplasia?

Answer 29

Follicular hyperplasia is caused by stimuli that activate humoral immune responses.

Folllicular: Humoral response

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Question 30

Describe follicular hyperplasia.

Answer 30

It is defined by the presence of large oblong germinal centers (secondary follicles), which are
surrounded by a collar of small resting naive B cells (the mantle zone) ( Fig. 13-3 ).

Germinal centers are normally polarized into two distinct regions:

• (1) a dark zone containing proliferating blastlike B cells (centroblasts) and
• (2) a light zone composed of B cells with irregular or cleaved nuclear contours (centrocytes).
• Interspersed between the germinal B centers is an inconspicuous network of antigen-presenting follicular dendritic cells and macrophages (often referred to as tingible-body macrophages) containing the nuclear debris of B cells, which undergo apoptosis if they fail to produce an antibody with a high affinity for antigen

Question 31

Germinal centers are normally polarized into two distinct regions:

Answer 31

(1) a dark zone containing proliferating blastlike B cells (centroblasts) and
(2) a light zone composed of B cells with irregular or cleaved nuclear contours (centrocytes).

Question 32

What is interspersed between the germinal B centers?

Answer 32

Interspersed between the germinal B centers is an inconspicuous network of antigen-presenting follicular dendritic cells and macrophages (often referred to as tingible-body macrophages) containing the nuclear debris of B cells, which undergo apoptosis if they fail to produce an antibody with a high affinity for antigen

Question 33

What are tingible-body macrophages?

Answer 33

Interspersed between the germinal B centers is an inconspicuous network of antigen-presenting follicular dendritic cells and macrophages (often referred to as tingible-body macrophages) containing the nuclear debris of B cells, which undergo apoptosis if they fail to produce an antibody with a high affinity for antigen

Question 34

What are the causes of follicular hyperplasia?

Answer 34

Causes of follicular hyperplasia include:

• rheumatoid arthritis,
• toxoplasmosis, and
• early stages of infection with HIV.

This form of hyperplasia is morphologically similar to follicular lymphoma (discussed later).

Question 35

What are the features favoring a reactive (non-neoplastic) hyperplasia include

Answer 35

Features favoring a reactive (non-neoplastic) hyperplasia include

• (1) preservation of the lymph node architecture, including the interfollicular T-cell zones and the sinusoids;
• (2) marked variation in the shape and size of the follicles; and
• (3) the presence of frequent mitotic figures, phagocytic macrophages, and recognizable light and dark zones, all of which tend to be absent from neoplastic follicles.

Question 36

What causes Paracortical hyperplasia?

Answer 36

Paracortical hyperplasia is caused by stimuli that trigger T cell–mediated immune responses, such as acute viral infections (e.g., infectious mononucleosis).

Paracortical: Cell-mediated

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Question 37

What is the apperance of Paracortical hyperplasia?

Answer 37

The T-cell regions
typically contain:

• immunoblasts,
• activated T cells three to four times the size of resting lymphocytes that have round nuclei,
• open chromatin, several prominent nucleoli, and
• moderate amounts of pale cytoplasm.

The expanded T-cell zones encroach on and, in
particularly exuberant reactions, efface the B-cell follicles. In such cases immunoblasts may
be so numerous that special studies are needed to exclude a lymphoid neoplasm.

In
addition, there is often a hypertrophy of sinusoidal and vascular endothelial cells, sometimes
accompanied by infiltrating macrophages and eosinophils.

Question 38

What is Sinus histiocytosis (also called reticular hyperplasia)?

Answer 38

Sinus histiocytosis (also called reticular hyperplasia) refers to an **increase in the
number and size of the cells that line lymphatic sinusoids.**

Although nonspecific, this form of
hyperplasia may be particularly prominent in lymph nodes draining cancers such as
carcinoma of the breast.

Question 39

Sinus histiocytosis (also called reticular hyperplasia) may be particularly prominent in what?

Answer 39

Although nonspecific, this form of
hyperplasia may be particularly prominent in lymph nodes draining cancers such as
carcinoma of the breast.

Question 40

What is the morphological appearance of Sinus histiocytosis (also called reticular hyperplasia)

Answer 40

The lining lymphatic endothelial cells are markedly hypertrophied and macrophages are greatly increased in numbers, resulting in the expansion and
distension of the sinuses

Question 41

Answer 41

FIGURE 13-3 Follicular hyperplasia.

• A, Low-power view showing a reactive follicle and surrounding mantle zone. The dark-staining mantle zone is more prominent adjacent to the germinal-center light zone in the left half of the follicle. The right half of the follicle consists of the dark zone.
• B, High-power view of the dark zone shows several mitotic figures and numerous macrophages containing phagocytosedapoptotic cells (tingible bodies).

Question 42

What is the characterisitc of lymph node in chronic reactions?

Answer 42

Characteristically, lymph nodes in chronic reactions are :

• nontender, because nodal enlargement occurs slowly over time.

Question 43

Chronic lymphadenitis is particularly common where?

Answer 43

Chronic lymphadenitis is particularly common in inguinal and axillary nodes, which drain relatively large areas of the body and are challenged frequently.

Question 44

Chronic immune reactions can promote the appearance of organized collections of immune cells in
nonlymphoid tissues.

T or F

Answer 44

True

Before leaving the reactive disorders of lymphocytes, it is worth pointing out that chronic immune reactions can promote the appearance of organized collections of immune cells in nonlymphoid tissues.

Question 45

What is the classic example of reactive disorders of lymphocytes that chronic immune reations can promote the appearance of organized collections of immune cells in nonlymphoid tissues?

Answer 45

• A classic example is seen in chronic gastritis caused by Helicobacter pylori, in which aggregates of mucosal lymphocytes are seen that simulate the appearance of Peyer’s patches.
• A similar phenomenon occurs in rheumatoid athritis, in which B-cell follicles often appear in the inflamed synovium.
• Lymphotoxin, a cytokine required for the formation of normal Peyer’s patches, is probably involved in the establishment of these “extranodal” inflammation-induced collections of lymphoid cells.